Hemodynamic-GUIDEd management of Heart Failure (GUIDE-HF)

In that study, incremental reductions in the PA pressures in the monitored arm were associated with both reduction in the frequency of HFH and improvements in health-related quality of life among patients with both preserved (HFpEF) and reduced ejection fraction (HFrEF).3,4 Additionally, hemodynamic-guided HF management in the subset of HFrEF patients treated with guideline-directed medical therapy (GDMT) was associated with a strong trend toward improved survival compared to traditional clinical management.4,7 Consistent benefit is demonstrated in several retrospective studies from the CHAMPION Trial.10-13 as well as extensive analysis of “real-world� experience.6,14 and in Medicare claims data managed in a commercial setting.5,15 Whether the benefits of PA pressure guided therapy can be extended to a broader pool of patients with milder (NYHA class II) or more severe (NYHA class IV) HF or to those without recent hospitalization for HF but with elevation in natriuretic peptide levels remains unclear. Remotely uploaded PA pressure information from the control group will be blocked from investigator review. [...]other than medication changes resulting from information from RHC procedures, control group subjects will not have pressure-based medication changes over time and should be managed instead according to routine practice as informed by published clinical guidelines. Thresholds for NT-proBNP/BNP corrected for BMI using a 4% reduction per BMI unit over 25 kg/m2 Subjects ≥18 y of age able and willing to provide informed consent Chest circumference of 15) at implant RHC, a history of noncompliance, or any condition that would preclude CardioMEMS PA Sensor implantation Table I Inclusion and exclusion criteria PA pressure goals PA diastolic: 8-20 mm Hg PA mean: 10-25 mm Hg PA systolic: 15-35 mm Hg Optimization phas

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Informing the NHS Outcomes Framework : evaluating meaningful health outcomes for children with neurodisability using multiple methods including systematic review, qualitative research, Delphi survey and consensus meeting

Background: The identification of suitable outcome measures will improve the evaluation of integrated NHS care for the large number of children affected by neurodisability, and has the potential to encourage the provision of more appropriate and effective health care. This research sought to appraise the potential of patient-reported outcome measures (PROMs) for children and young people with neurodisability. Aim: This research aimed (i) to identify key outcomes of health care for children with neurodisability, beyond morbidity and mortality, from the perspectives of children, parents and professionals, (ii) to critically appraise existing generic multidimensional PROMs, and (iii) to examine whether or not the key outcomes might be measured by existing PROMs. We also sought agreement on a definition of neurodisability. Methods: Data were gathered in three main ways, (i) a systematic review identified eligible generic multidimensional PROMs and peer-reviewed studies evaluating psychometric performance using English-language questionnaires. Studies were appraised for methodological quality and psychometric performance was appraised using standard criteria. (ii) Focus groups and interviews with children and young people with neurodisability, and separately with parents, sought to identify important outcomes of NHS care, and their feedback on example PROM questionnaires. (iii) An online Delphi survey was conducted with a multidisciplinary sample of health professionals to seek agreement on appropriate NHS outcomes. In addition, we convened a consensus meeting with a small nominal group of young people, parents and professionals, the group sought agreement on a core set of important health outcomes. Results: From the systematic review, we identified 126 papers that reported eligible evidence regarding the psychometric performance of 25 PROMs. Evidence of psychometric robustness was more favourable for a small number of PROMs: KIDSCREEN (generic), DISABKIDS (chronic-generic) and Child Health Utility 9D (preference-based measure). The Pediatric Quality of Life Inventory and KINDL offer both self-report and a proxy report version for a range of age bands, but evidence of their psychometric performance was weaker. Evidence was lacking in one or more respects for all candidate PROMs, in both general populations and those with neurodisability. Proxy reporting was found generally to be poorly correlated with self-report. Focus groups and interviews included 54 children and young people, and 53 parents. The more important health outcomes were felt to be communication, emotional well-being, pain, mobility, independence/self-care, worry/mental health, social activities and sleep. In addition, parents of children with intellectual impairment identified behaviour, toileting and safety as important outcomes. Participants suggested problems with the face validity of example PROM questionnaires for measuring NHS care. In the Delphi survey, 276 clinicians from a wide range of professions contributed to at least one of four rounds. Professionals rated pain, hearing, seeing, sleep, toileting, mobility and communication as key goals for the NHS but also identified treating neurological symptoms as important. Professionals in the Delphi survey and parents working with the research team agreed a proposed definition for neurodisability. The consensus meeting confirmed overlap between the outcomes identified as important by young people, parents and professionals, but not complete agreement. Conclusions: There was agreement between young people, parents and professionals regarding a core suite of more important health outcomes: communication, emotional well-being, pain, mobility, independence/self-care, worry/mental health, social activities and sleep. In addition, behaviour, toileting and safety were identified as important by parents. This research suggests that it would be appropriate to measure these constructs using PROMs to assess health care. None of the candidate PROMs in the review adequately captures all of the identified constructs, and there is inadequate evidence that candidate PROMs are psychometrically robust for use across children with neurodisability. Further consultation with young people, families and professionals is warranted to support the use of PROMs to measure NHS outcomes. Research to test potential PROMs with different age groups and conditions would be valuable

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Combining TMS and EEG for Characterizing Motor Network Interactions and Improving Motor Recovery after Stroke

University of Minnesota Ph.D. dissertation. December 2016. Major: Biomedical Engineering. Advisor: Bin He. 1 computer file (PDF); viii, 109 pages.Imaging of electrophysiological activity within the brain is crucial to understanding function in both healthy and disease conditions. The overall goal of this dissertation is to use both non-invasive neuromodulation and non-invasive neuroimaging to characterize and manipulate underlying neurological network dynamics in both healthy and stroke affected subjects. The two main applications of work are for the evaluation of peripheral motor activity on motor network dynamics in healthy subjects, and as a brain-based treatment for motor recovery after stroke. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) imaging can be used to analyze cortical reactivity and connectivity of underlying brain networks. However, the effect of corticospinal and peripheral muscle activity on TMS-evoked potentials (TEPs), particularly in motor areas, is not well understood. One aim of the present dissertation is to evaluate the relationship between cortico-spinal activity, in the form of peripheral motor-evoked potentials (MEPs), and the TEPs from motor areas, along with the connectivity among activated brain areas. This research demonstrates that TMS-EEG, along with adaptive connectivity estimators, can be used to evaluate the cortical dynamics associated with sensorimotor integration and proprioceptive manipulation. Stroke is a devastating neurological disorder which can result in lasting impairment affecting quality-of-life. Combining contralesional repetitive TMS (rTMS) with EEG-based brain-computer interface (BCI) training can address motor impairment after stroke by down-regulating exaggerated inhibition from the contralesional hemisphere and encouraging ipsilesional activation. Another aim of this dissertation was to evaluate the efficacy of combined rTMS+BCI, compared to sham rTMS+BCI, and BCI alone, on motor recovery after stroke in subjects with lasting motor paresis. As evaluated in a series of stroke patients, such a brain-based neuromodulatory and imaging approach for rehabilitation could potentially lead to greater understanding of the influence of brain network dynamics in recovery and design of optimal treatment strategies for individual patients. Our findings demonstrate the feasibility and efficacy of not only combined rTMS+BCI but also BCI alone, as demonstrated by significant improvements over time in behavioral and electrophysiological measures. In summary, the present dissertation research developed and evaluated the combination of neuromodulation and neuroimaging for the non-invasive mapping of motor network activities in the diseased and normal brain. Evaluations were conducted in healthy controls to evaluate the influence of peripheral muscle activity on resulting neural network activity, as well as in stroke patients to provide a brain-based treatment for motor rehabilitation. The results obtained suggest the importance of non-invasive spatiotemporal neuroimaging, along with non-invasive neuromodulation, for providing insight into neuroscience questions and providing novel treatments for clinical problems in a brain-based manner

The influence of corticospinal activity on TMS-evoked activity and connectivity in healthy subjects: A TMS-EEG study.

Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) can be used to analyze cortical reactivity and connectivity. However, the effects of corticospinal and peripheral muscle activity on TMS-evoked potentials (TEPs) are not well understood. The aim of this paper is to evaluate the relationship between cortico-spinal activity, in the form of peripheral motor-evoked potentials (MEPs), and the TEPs from motor areas, along with the connectivity among activated brain areas. TMS was applied to left and right motor cortex (M1), separately, at motor threshold while multi-channel EEG responses were recorded in 17 healthy human subjects. Cortical excitability and source imaging analysis were performed for all trials at each stimulation location, as well as comparing trials resulting in MEPs to those without. Connectivity analysis was also performed comparing trials resulting in MEPs to those without. Cortical excitability results significantly differed between the MEP and no-MEP conditions for left M1 TMS at 60 ms (CP1, CP3, C1) and for right M1 TMS at 54 ms (CP6, C6). Connectivity analysis revealed higher outflow and inflow between M1 and somatosensory cortex bi-directionally for trials with MEPs than those without for both left M1 TMS (at 60, 100, 164 ms) and right M1 TMS (at 54, 100, and 164 ms). Both TEP amplitudes and connectivity measures related to motor and somatosensory areas ipsilateral to the stimulation were shown to correspond with peripheral MEP amplitudes. This suggests that cortico-spinal activation, along with the resulting somatosensory feedback, affects the cortical activity and dynamics within motor areas reflected in the TEPs. The findings suggest that TMS-EEG, along with adaptive connectivity estimators, can be used to evaluate the cortical dynamics associated with sensorimotor integration and proprioceptive manipulation along with the influence of peripheral muscle feedback

TEPs for right M1 stimulation for MEP and no-MEP trials.

<p>(Upper) Butterfly plot of the average TMS-evoked activity from all electrodes (average of 11 participants with simultaneous EMG recording) for trials with an MEP (left) and those without (right). Red line indicates Cz electrode. Timing of the peaks is indicated by vertical dashed lines. (Lower) Voltage distributions and cortical current density estimates of the TMS-evoked activity for each peak in the Cz waveform. The blue boxes and asterisks highlight the 54ms latency, for which the topography significantly differed between the <i>MEP</i> and <i>no-MEP</i> conditions for electrodes CP6 and C6 (<i>p<0</i>.<i>05</i>).</p

Inflow and outflow amongst ROIs for right M1 stimulation.

<p>Five ROIs were selected (left) using the cortical current density estimates for each latency (average of 11 participants with simultaneous EMG recording). The ROI corresponding to the stimulation target is indicated with a white x. Time-varying connectivity, as measured by aDTF, was calculated for each of the five ROIs for trials containing MEPs (middle column) and trials without MEPs (right column), including both outflow (top row) and inflow (bottom row) patterns.</p